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ARTIGOS ORIGINAIS | ORIGINAL ARTICLES
Use of CD25 as an immunohistochemical marker
for acquired ocular toxoplasmosis
Uso do CD25 como um marcador imuno-histoquímico de toxoplasmose ocular adquirida
CRISTINA MIYAMOTO 1,2 , RUBENS BELFORT MATTOS NETO 2 , SEBASTIAN DI CESARE 1 , RUBENS BELFORT JUNIOR 2 , MIGUEL N. BURNIER JR. 1,2
ABSTRACT
Purpose: Toxoplasmosis is the most common cause of posterior infectious
uveitis worldwide. It is often impossible to determine its congenital or acquired
nature. Interleukin-2 (IL-2) in peripheral blood has been described as a possible
marker for acquired toxoplasmosis. The purpose of this study is to evaluate the
histopathological characteristics of ocular toxoplasmosis cases using CD25 as
a marker for the expression of interleukin-2.
Methods: Ten formalin-fixed, paraffin-embedded enucleated globes from ten
immunocompetent patients with clinical diagnosis of toxoplasmosis were
evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive
IgM) while six were IgM negative and IgG positive for toxoplasmosis. Histopathological
slides were reviewed for the extension of the retinal necrosis,
number of toxo cysts, the granulomatous inflammatory reaction, the presence
of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry
using monoclonal antibodies was performed to observe the expression of
CD4, CD8, CD20, CD25, and CD68.
Results: The histopathological evaluation disclosed no differences between
acquired and the other ocular toxoplasmosis cases regarding the characteristics
studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired
cases of ocular toxoplasmosis compared to the remainders.
Conclusions: To the best of our knowledge, this is the first report showing that
the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular
toxoplasmosis.
Keywords: Toxoplasmosis, ocular/immunology; Immunohistochemistry, Toxoplasmosis,
ocular/congenital; Toxoplasmosis, ocular/diagnosis; Interleukon-2/
diagnostic use; Antigens, CD5; Diagnosis, differential; Antigens, differentiation
RESUMO
Objetivo: Toxoplasmose é a causa mais comum de uveíte posterior no mundo.
Em grande parte dos casos, não é possível determinar se a doença ocular é
devida a um quadro congênito ou adquirido. Interleucina-2 (IL-2) no sangue
periférico foi descrita como um possível marcador de toxoplasmose adquirida.
O objetivo deste estudo foi avaliar as características de casos de toxoplasmose
usando CD25 como um marcador da expressão de interleucina-2.
Métodos: Dez olhos enucleados fixados com formalina e embebidos em parafina
de dez pacientes imunocompetentes com diagnóstico clínico de toxoplasmose
ocular foram examinados. Quatro pacientes tinham a forma adquirida
(IgM positivo) enquanto 6 eram IgM negativo e IgG positivo para toxoplasmose.
Cortes histopatológicos foram avaliados quanto a extensão de
necrose retiniana, número de cistos de T. gondii, reação granulomatosa e
presença de células B e T na coróide, bem como a expressão de interleucina-
2. Estudo imuno-histoquímico utilizando anticorpos monoclonais foi realizado
para determinar a expressão de CD4, CD8, CD20, CD25 e CD68.
Resultados: A avaliação histopatológica não mostrou diferenças entre os
casos de toxoplasmose ocular com relação às características avaliadas mencionadas
anteriormente. Entretanto, CD25 revelou maior expressão de interleucina-2
nos 4 casos adquiridos comparado com os demais.
Conclusões: Expressão elevada de CD25 foi encontrada em todos os casos de
toxoplasmose ocular adquirida. Assim, o uso de CD25 como marcador da
interleucina-2 pode ser uma ferramenta útil para diferenciar toxoplasmose
ocular congênita de adquirida.
Descritores: Toxoplasmose ocular/imunologia; Imuno-histoquímica; Toxoplasmose
ocular/congênito; Toxoplasmose ocular/diagnóstico; Interleucina-2/uso
diagnóstico; Antígenos CD5; Diagnóstico diferencial; Antígenos de diferenciação
INTRODUCTION
T
oxoplasmosis is caused by the intracellular protozoan Toxoplasma
gondii (1) , that infects up to a third of the world’s
population (2) . Infections may be acquired congenitally or
through the ingestion or handling of undercooked or raw infected
meat, contaminated vegetables or water (1-3) . The disease is
asymptomatic in many immunocompetent hosts, however
ocular lesions may be present in up to 20% of infected individuals
(1) . In immunocompromised patients, the disease often
manifests as encephalitis and also ophthalmic lesions (4-6) .
Ocular involvement occurs in either congenital or acquired
infection. In the United States, infection occurs in 2/1000
Work carried out at the Department of Ophthalmology, Federal University of São Paulo and
Mc Gill University, Canada.
1
Physician, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Canada.
2
Physician, Departament of Ophthalmology, Universidade Federal de São Paulo - UNIFESP,
São Paulo (SP), Brazil.
Correspondence address: Cristina Miyamoto, Departament of Ophthalmology Universidade
Federal de São Paulo. Rua Botucatu, 821 - 2º Andar - São Paulo (SP) - CEP 04023-062
E-mail: crismiyamoto@yahoo.com
Recebido para publicação em 28.04.2010
Última versão recebida em 09.08.2010
Aprovação em 23.10.2010
pregnancies, with a transplacental infection rate ≤ 50% (6-7) . In
France, the estimated yearly incidence of contamination in
women during pregnancy is 6-7/1000 and of congenital toxoplasmosis
is approximately 0.1% of births (8) . Seventy percent of
infants with congenital infection show chorioretinal scars (7) .
Although most of the cases in adults were thought to be a
consequence of the reactivation of congenital lesions (9) , several
studies indicate that ocular disease may be caused by T. gondii
infection after birth (1,6,10-12) . In fact, most cases in Brazil are a consequence
of post-natal infection (6) .
Ocular toxoplasmosis is characterized by a necrotizing
retinitis with oval or circular lesions (4) . It is often impossible to
determine the congenital or acquired nature of this particular
uveitic process (1-2,13-15) . Late onset acquired ocular toxoplasmosis
may manifest itself up until at least thirteen years after primary
infection (16 -17) .
Interleukin-2 (IL-2) plays an important role in the proliferation
and survival of recently activated effector T cells (18) . IL-2
in peripheral blood has been described as a possible marker for
acquired toxoplasmosis (7) . Yamamoto et al. evaluating blood
samples from 136 subjects with positive and negative titers of
antibody (IgM and IgG) to T. gondii, found that production of
IL-2 and interferon-g by peripheral blood mononuclear cells
Arq Bras Oftalmol. 2010;73(5):443-6 443